IN A PREVIOUS PAPER, WE INTRODUCED A NOVEL IN VIVO TECHNIQUE TO QUANTIFY GLUCOSE TRANSPORT IN HUMAN FOREARM MUSCLE TISSUE. THAT APPROACH WAS BASED ON THE MULTIPLE TRACER DILUTION TECHNIQUE: DIFFERENT TRACER WITH DIFFERENT MOLECULAR CHARACTERISTICS A RE SIMULTANEOUSLY INJECTED IN ORDER TO SEPARATELY MONITOR THE KINETIC EVENTS. IN THE STUDY 12C-MANNITOL, WHICH IS NOT TRANSPORTABLE IN THE CELL, AND 3-O-14 C-METHYL-D-GLUCOSE, NOT METABOLIZABLE, WERE INJECTED AND A COMPARTMENTAL MODEL WAS DEVELOPED TO DESCRIBE SIMULTANEOUSLY THE TWO TRACER CURVES. THE MODEL WELL DESCRIBES HETEROGENEITY OF BLOOD FLOW WITHIN THE DEEP FOREARM TISSUES AND PROVIDES RATE CONSTANTS OF TRANSMEMBRANE INWARD AND OUTWARD 3-O-14C-METHYL-D-GLUCOSE TRANSPORT. IN THIS YEAR, WE HAVE EXTENDED THE MULTICOMPARTMENTAL MODEL FOR THE ANALYSIS OF A NEW TRIPLE TRACER PROTOCOL. THE IDENTIFICATION OF THIS TRACER MODEL ALLOWS TO ESTIMATE NOT ONLY THE RATES OF TRANSMEMBRANE GLUCOSE TRANSPORT, AS THE PREVIOUS MODEL, BUT ALSO THE RATE OF INTRACELLULAR GLUCOSE PHOSPHORYLATION. FURTHER, BY ASSUMING KNOWN THE ARTERIAL GLUCOSE INFLUX FROM THE MEASURED BLOOD FLOW AND BLOOD GLUCOSE CONCENTRATION, WE HAVE CALCULATED THE EXTRACELLULAR AND INTRACELLULAR MASSES, THE INWARD AND OUTWARD TRANSMEMBRANE GLUCOSE FLUXES, THE PHOSPHORYLATION GLUCOSE FLUX, THE EXTRACELLULAR AND INTRACELLULAR VOLUMES, AND THE EXTRACELLULAR AND INTRACELLULAR CONCENTRATIONS. ALL THESE PARAMETERS HAVE BEEN CALCULATED UNDER BOTH BASAL AND PHYSIOLOGIC HYPERINSULINEMIC CONDITIONS. THIS MODEL HAS BEEN ALSO USED TO STUDY TYPE 2 (NON-INSULIN-DEPENDENT) DIABETIC SUBJECTS IN ORDER TO ASSESS THE RELATIVE ROLE OF GLUCOSE TRANSPORT AND PHOSPHORYLATION IN DETERMINING INSULIN RESISTANCE. FINALLY THE MODEL HAS BEEN APPLIED TO STUDY SUBJECTS OF INSULIN RESISTANT, NORMAL GLUCOSE TOLERANT OFFSPRING OF TWO NIDDM PARENTS TO INVESTIGATE WHETHER TRANSMEMBRANE GLUCOSE TRANSPORT AND GLUCOSE PHOSPHORYLATION IN VIVO ARE IMPAIRED AND CONTRIBUTE TO INSULIN RESISTANCE. WORK IS IN PROGRESS WITH A NEW EXPERIMENTAL PROTOCOL INVOLVING AN ADDITIONAL FOURTH TRACER WHICH IS CONFINED IN THE INTRAVASCULAR SPACE.